INTRODUCTION
Asymptomatic bacteriuria, defined as at least 105 CFU/mL uropathogen isolated in a sterile urine sample without symptoms of urinary tract infection (UTI), is a common condition in the community (1). Its incidence is estimated at 1%-5% in healthy premenopausal women, 4%-19% in healthy older women and men, 0.7%-27% in patients with diabetes mellitus, 2%-10% in pregnant women, 15%-50% in the older population in healthcare settings, and increases up to 23%-89% in patients with spinal cord injury (1). Asymptomatic bacteriuria (ASB) is often misdiagnosed as UTI, although it does not require treatment (2). Morbidity attributable to bacteriuria is defined only for pregnant women and patients scheduled for invasive urological procedures accompanied by mucosal trauma. Guidelines recommend against treating ASB with antibiotics because randomized trials demonstrated no clinical benefit (1). The harms of unnecessary antimicrobial use have been documented, including antibiotic-associated diarrhea, increased drug resistance to microorganisms, adverse drug reactions, and increased healthcare costs, respectively (3). Despite national guidelines recommending against antibiotic therapy for ASB, high-antibiotic treatment rates continue (4-7). Most of the antibiotics are prescribed within the scope of outpatient services (8,9). The literature shows that unnecessary broad-spectrum antibiotic use is common in outpatient centers (10).
Our study analyzes the approaches of primary care physicians to ASB through an internet-based questionnaire.
METHODS
Due to the lack of a central system and lack of documentation in our country, the diagnosis and treatment of diseases cannot be fully evaluated. Thus, we planned to evaluate the inappropriate treatment of UTI, which is common, by questionnaires of primary care physicians.
In this study conducted between May-August 2020, family physicians working in family health centers in Istanbul and health workers work as family medicine specialists and residents in training-research hospitals were included. According to the data of the medical chambers in Istanbul, there were 4,500 family physicians, and in our study, the number of cases to be taken to achieve 80% power at the a: 0.05 level was calculated as at least 354. A form that was created to evaluate the descriptive features, urinalysis-urine culture conditions and the treatments administered was used as a data collection tool. To determine the descriptive features, questions were asked to evaluate age, gender, workplace, tenure (year), in which cases urinalysis and urine culture were requested, and if so, what treatment was administered.
Data collection tools were prepared on Google forms and delivered to healthcare professionals online, and responses were collected in the same way. An invitation was sent to all participants using email on May 1, 2020, and the answers given until August 31, 2020, were recorded. All participants were informed before they started to fill out the form, and two options were presented on the informed consent page (yes/no). Only those who chose yes were included in this study. Due to the design of the questionnaire, all questions must be answered to ensure successful participation. In this study, 436 physicians who gave consent to participate in the study were included. It was accepted that no intervention that could disrupt the mucosal integrity of the urinary system would be planned in the primary care setting. The examinations and treatments performed on the asymptomatic patient, except for pregnancy, were evaluated as inappropriate.
Ethics statement: The methodology and questionnaire for this study were approved by the of University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital Ethics Committee (decision no: 2021-04-15, date: 15.02.2021). The authors assert that all procedures contributing to this work comply with the ethical standards of University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital and the Helsinki Decleration of 1975, as revised in 2008. The participants’ consent to parcipate in the study was requested personally from each individual.
Statistical Analysis
The NCSS (Number Cruncher Statistical System) program was used for statistical analysis. Descriptive statistical methods (frequency, percentage) were used while evaluating the data. The Pearson chi-square test was used to compare qualitative data, Fisher’s Exact test and Fisher-Freeman-Halton test were used for categorical variables. Statistical significance was set as p<0.05.
RESULTS
This study was conducted with 436 family physicians; 55.5% (n=242) of them were females and 44.5% (n=194) males. 56% (n=244) of the physicians participating in this study were between the ages 25-35, 26.6% (n=116) were between the ages of 35-45, 14.7% (n=64) were between the ages of 45-55 and 2.8% (n=12) were from 55-65 years old.
It was observed that 34.4% (n=150) of the physicians participating in this study worked as resident family physicians, 22% (n=96) contracted family medicine specialists (CFMS), 34.9% (n=152) family physicians and 8.7% (n=38) were specialist family physicians.
It was observed that 59.6% (n=260) of the physicians were assigned to family health centers, 40.4% (n=176) to secondary and tertiary hospitals and 63.8% (n=278) of the physicians had 0-10 years of professional experience, 20.2% (n=88) had 10-20 years, 13.3% (n=58) had a 20-30-year period and 2.8% (n=12) had more than 30 years (Table 1).
They were asked, “in which situations would you like to have a urine test?” and the answers given by the physicians to the question were as follows: 85.3% (n=372) in case of pregnancy, 83% (n=362) when the systemic infection is suspected, 66.9% (n=292) in the presence of a urinary catheter, 29.8% (n=130) were in advanced age, 38.9% (n=170) from those with chronic disease and 91.7% (n=400) from patients with urinary symptoms.
While 4.1% (n=18) of the physicians stated that they wanted routine urine culture and urinalysis, 95.9% (n=418) stated that they did not. Of the physicians who did not want a routine urine culture with urinalysis, 42.1% (n=176) stated that they wanted a routine urine culture from the patients with urinary symptoms, 32.5% (n=136) from those with chronic disease, 34% (n=142) from those who were pregnant, 70.3% (n=294) from those who had a urinary catheter, 18.2% (n=76) from those with advanced age and 23.4% (n=98) from those with other reasons.
While 46.8% (n=204) of the physicians stated that they wanted a culture from the patient who had urine examination (+) and had no urinary symptoms, 53.2% (n=232) stated that they did not want a culture. 91.3% (n=398) of the physicians stated that they gave treatment to patients who had positive urinalysis or culture (+) and had no urinary symptoms.
The findings showed that 79.9% (n=318) of the physicians used fosfomycin in the treatment, 44.7% (n=178) nitrofurantoin, 21.1% (n=84) quinolone, 13.6% (n=54) sulfonamide, 3.5% (n=14) penicillin, 21.1% (n=84) cephalosporin and 6% (n=24) other agents (Table 2).
There was no statistically significant difference between the distribution of the physicians’ treatment-giving status according to age groups (p>0.05).
A statistically significant difference was found between the distribution of the physicians’ treatment-giving status by gender. The rate of administering the necessary treatment by female physicians was significantly higher than that of male physicians (p=0.001; p<0.01).
A statistically significant difference was found between the distribution of the treatment status of the physicians according to their duties. The rate of administering the necessary treatment among specialist family physicians was significantly higher than in those with CFMS. Additionally, the rate of administering unnecessary treatment in those with CFMS and family physicians was significantly higher than in those with a family physician resident and family physician specialist (p=0.001; p<0.01).
A statistically significant difference was found between the distribution of the treatment status of the physicians according to their workplace. The rate of administering unnecessary treatment by physicians whose workplace was a family health center was significantly higher than that of physicians whose workplace was a hospital (p=0.001; p<0.01).
A statistically significant difference was found between the distribution of the treatment status of the physicians according to their tenure. The rate of providing necessary treatment for physicians with 20-30 years of tenure was significantly lower than those of physicians with a tenure of between 0 and 10 and 10-20 years (p=0.001; p<0.01) (Table 3).
DISCUSSION
The evaluation and improvement of antibiotic administration in outpatient treatment is a major issue. According to the data of the American Centers for Disease Control and Prevention, nearly 80% of antibiotic prescriptions are given in outpatient centers and it is reported that 30% of these prescriptions are unnecessary (11).
UTI is one of the most common infections for which antimicrobials are prescribed, and likewise, most patients prescribed antimicrobial agents do not require treatment (12). This is also true for ASB, which has proven to have a high prevalence, such as women, tuberculosis patients, and older people (13). The overtreatment of ASB may lead to many undesirable consequences, such as the disruption of intestinal flora, which increases the risk of Clostridium difficile infection, antibiotic resistance, and increased healthcare-related costs (5,14). Additionally, unnecessary antimicrobial therapy may lead to the development of symptomatic urinary infections by affecting low virulence strains that inhibit the development of uropathogens (15,16).
Guidelines report that diagnosis and treatment of ASB may be beneficial only in two groups of patients: pregnant women and patients scheduled for urological procedures at risk of mucosal disruption. Except for these patients, they strongly recommend that ASB not be screened or treated with antimicrobials (12).
Studies have shown that the prevalence of this inappropriate treatment ranges from 45% to 83% (17). The American Geriatrics Society and the American Foundation of Internal Medicine reported the unnecessary use of antimicrobials for ASB as one of the top five overused services in the “Choose Wisely Campaign” (18). In our study, the findings showed that the rate of inappropriate requests for urinalysis and culture was high. It was seen that high rates of urine examination were requested in cases where screening was not recommended, such as the presence of a urinary catheter, advanced age, and chronic disease. Given that 91.3% (n=398) of the physicians stated that they would administer treatment to patients who had (+) infection in urinalysis or culture and did not have urinary symptoms, inappropriate treatment is generally administered based on simple urine measurement strip results.
Urinalysis or microbiology cannot distinguish ASB from symptomatic UTI. Therefore, guidelines recommend the presence of two or more signs of UTI (such as dysuria, urgency urinate, frequent urination, flank pain or suprapubic pain) as the most accurate indication for diagnosis. Guidelines are against the use of urine dipstick tests and recommend urine culture only if there are signs and symptoms for prescribing antibiotics (19). The UK’s National Institutes of Health and Clinical Excellence quality standard for elderly adults (QS260) also recommends diagnosing UTI with a complete clinical evaluation rather than urine test result due to varying accuracy (20).
If the urinalysis or culture is positive, it has been stated that 79.9% (n=318) of the participants used fosfomycin in the treatment, 44.7% (n=178) nitrofurantoin, 21.1% (n=84) cephalosporin, 21.1% (n=84) used quinolones, 13.6% (n=54) sulfonamides, 3.5% (n=14) penicillin and 6% (n=24) other agents. Fosfomycin and nitrofurantoin, which should be used as the first choice for treating uncomplicated UTI according to the guidelines, were also the most preferred agents in our study. Although appropriate agents are preferred regarding approach to the infection, it makes us think that the main problem here is the necessity of diagnosing UTI and correcting the choice of treatment. Reasons, such as a lack of clinical distinction between ASB and UTI, presence of non-specific symptoms or comorbid conditions, excessive reliance on urinalysis with pyuria/nitrite positivity/high bacterial counts, are important in explaining overtreatment. In another survey of physicians, decision-making based solely on laboratory findings was the most common reason for overtreatment (4,21-23).
In the first step, ASB treatment can only be considered an appropriate approach for pregnant women. In the evaluation made regarding demographic characteristics, the rate of appropriate approach in primary care physicians with relatively high tenure was significantly lower than in other physicians. Additionally, the rate of appropriate treatment by family physician specialists was significantly higher than that with CFMS. Unnecessary treatment rates of those who worked in the CFMS program and family physicians were significantly higher than those of family medicine residents and specialists. In this respect, it is seen that continuing education and following the guidelines are important regarding an appropriate approach.
In a systematic review investigating the inappropriate management of patients with ASB, it was reported that most interventions aimed at minimizing the rate of improper treatment were successful and resulted in a 25%-80% decrease in improper treatment (5). Over-reliance on urinalysis appears to result in improper antibiotic prescribing for ASB. Interestingly, difficulties in reducing inappropriate treatment of ASB can be overcome, as relatively simple interventions (educational and/or organizational) reduce the rate of improper antimicrobial prescribing.
CONCLUSION
In conclusion, clinical practice in the approach to ASB appears to be in significant discord with evidence-based guidelines. Most cases of overtreatment of ASB underlie the approach based on laboratory results rather than the patient’s clinical condition. The available evidence suggests that a combination of educational and organizational interventions would help improve the distinction between symptomatic urinary infection and ASB and adherence to evidence-based guidelines, and that ASB should be in a priority group for antimicrobial management programs.
ETHICS
Ethics Committee Approval: The methodology and questionnaire for this study were approved by the of University of Health Sciences Turkey, Bakırköy Dr. Sadi Konuk Training and Research Hospital Ethics Committee (decision no: 2021-04-15, date: 15.02.2021). The authors assert that all procedures contributing to this work comply with the ethical standards of Bakırköy Dr. Sadi Konuk Training and Research Hospital and the Helsinki Decleration of 1975, as revised in 2008.
Informed Consent: The participants’ consent to parcipate in the study was requested personally from each individual.
Authorship Contributions
Concept: H.P., Ö.P., A.İ.T., Design: H.P., Ö.P., S.K., İ.E., A.İ.T., Data Collection or Processing: H.P., Ö.P., S.K., İ.E., T.K., Analysis or Interpretation: H.P., Ö.P., T.K., A.İ.T., Literature Search: H.P., S.K., İ.E., Writing: H.P., Ö.P., T.K., A.İ.T.
Conflict of Interest: No conflict of interest was declared by the authors.
Financial Disclosure: The authors declared that this study received no financial support.